Medicinal Biotechnology for Disease Modeling, Clinical Therapy, and Drug Discovery and Development

Duelen, Robin; Corvelyn, Marlies; Tortorella, Ilaria; Leonardi, Leonardo; Chai, Yoke Chin; Sampaolesi, Maurilio

doi:10.1007/978-3-030-22141-6_5

Cited by 7 publications

(6 citation statements)

References 190 publications

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“…Alternatively, organoids can be generated with the (i) suspension culture procedure accompanied by the use of spinner flasks or rotating bioreactors, which can be described as rotating cell culture systems (Nakano et al 2012;Qian et al 2018;Hoarau-Véchot et al 2018;Przepiorski et al 2018;Capowski et al 2019;Velasco et al 2020;Sander et al 2020); (ii) Air-liquid interface (ALI), where stem cells are exposed to culture medium on one side and to air on the other for maximizing the oxygen and nutrient supply (Takasato et al 2015;Neal et al 2018;Choi et al 2020;Lo et al 2020;Esser et al 2020;Gunti et al 2021); (iii) Magnetic levitation, which poses its bases in tagging cells with magnetic nanoparticles and then exposing them to a magnetic field that levitates them to the liquid-air interface where they aggregate and generate ECM components (Desai et al 2017;Tseng et al 2018;Ferreira et al 2019;Velasco et al 2020); (iv) 3D bioprinting, which could allow controlling the spatial positioning of cells and other biological components such as growth factors and ECM structural components (Fig. 3) (Duelen et al 2019;Reid et al 2019;Sun et al 2020;Kupfer et al 2020;Rawal et al 2021;Yang et al 2021).…”

Section: Organoidsmentioning

confidence: 99%

The role of physical cues in the development of stem cell-derived organoids

et al. 2021

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Organoids are a novel three-dimensional stem cells’ culture system that allows the in vitro recapitulation of organs/tissues structure complexity. Pluripotent and adult stem cells are included in a peculiar microenvironment consisting of a supporting structure (an extracellular matrix (ECM)-like component) and a cocktail of soluble bioactive molecules that, together, mimic the stem cell niche organization. It is noteworthy that the balance of all microenvironmental components is the most critical step for obtaining the successful development of an accurate organoid instead of an organoid with heterogeneous morphology, size, and cellular composition. Within this system, mechanical forces exerted on stem cells are collected by cellular proteins and transduced via mechanosensing—mechanotransduction mechanisms in biochemical signaling that dictate the stem cell specification process toward the formation of organoids. This review discusses the role of the environment in organoids formation and focuses on the effect of physical components on the developmental system. The work starts with a biological description of organoids and continues with the relevance of physical forces in the organoid environment formation. In this context, the methods used to generate organoids and some relevant published reports are discussed as examples showing the key role of mechanosensing–mechanotransduction mechanisms in stem cell-derived organoids.

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Section: Organoidsmentioning

confidence: 99%

The role of physical cues in the development of stem cell-derived organoids

et al. 2021

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“…With technological advances in the areas of molecular structure characterization, computational science and molecular biology, CADD is a promising avenue to facilitate the discovery, design and optimization of potential therapeutic agents in the era of big data. Not only does it reduce the time for drug discovery, CADD plays a prominent role in reducing the quantity of testing molecules in vitro or in vivo [115,116]. By predicting the numerous small molecules, either natural or synthetic compounds, that bind favorably to the target macromolecules, the number of trial experiments can be minimized.…”

Section: Computer-aided Drug Design (Cadd)-the Open Window Of Therapeutic Agentsmentioning

confidence: 99%

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Gandhi

Lee

et al. 2021

IJMS

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Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.

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“…Nevertheless, when somatic cells are reprogrammed to generate iPSCs, they acquire a series of new intrinsic properties that might generate hurdles in their applications. In fact, in addition to teratoma formation, karyotypic abnormalities and immature phenotype, they are characterized by unpredictable genetic background variations, thus making less reliable the corresponding disease model [42]. In this regard, genome editing tools enable creating isogenic controls iPSCs that differ from the original counterpart only on the gene/s responsible for the disease [43,44].…”

Section: Ex Vivo Stem Cell-based Modeling Systemsmentioning

confidence: 99%

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

Argentati

Tortorella

Bazzucchi

et al. 2020

JPM

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Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.Since their establishment, cell cultures have been proven to be the first and most powerful tool for the in vitro investigation of cell biology, from basic research to more complex translational approaches [6]. Classical two-dimensional (2D)-cultures usually consist of a unique type of cells (primary or continuous cultures) that grow in tissue culture polystyrene as adherent monolayers or in floating suspension, both in culture media that provide essential nutrients and growth factors. 2D-strategies are widely used to obtain a large number of cells, thus allowing the in vitro study of molecular mechanisms and development of metabolic assays [7-9]. However, due to their inability to recreate the in vivo complexity of the biological environment, they are not suitable for accurate disease modeling. These limitations have been overcome by the development of three-dimensional (3D)-cell cultures systems [10]. The rationale design of 3D-cell cultures is to harvest cells in microstructures that resemble tissues or organs shape and organization, thus allowing better cell-to-cell/cell-environment contacts and signaling crosstalk [11][12][13][14][15], essential events for tissues correct development and functioning [14,15]. The 3D-cell culture strategy is articulated in many different methods and techniques that can be grouped in scaffold-based or non-scaffold based platforms, each with particular advantages and disadvantages that make them useful for different applications [10,[16][17][18][19]. 3D-cell culture strategies are supported by the in silico...

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Medicinal Biotechnology for Disease Modeling, Clinical Therapy, and Drug Discovery and Development

Cited by 7 publications

References 190 publications

The role of physical cues in the development of stem cell-derived organoids

The role of physical cues in the development of stem cell-derived organoids

Drug Discovery of Spinal Muscular Atrophy (SMA) from the Computational Perspective: A Comprehensive Review

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

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